Publications
26 results found
Moser N, Yu L-S, Rodriguez Manzano J, et al., 2022, Quantitative detection of dengue serotypes using a smartphone-connected handheld Lab-on-Chip platform, Frontiers in Bioengineering and Biotechnology, Vol: 10, Pages: 1-14, ISSN: 2296-4185
Dengue is one of the most prevalent infectious diseases in the world. Rapid, accurate and scalable diagnostics are key to patient management and epidemiological surveillance of the dengue virus (DENV), however current technologies do not match required clinical sensitivity and specificity or rely on large laboratory equipment. In this work, we report the translation of our smartphone-connected handheld Lab-on-Chip (LoC) platform for the quantitative detection of twodengue serotypes. At its core, the approach relies on the combination of Complementary Metal Oxide-Semiconductor (CMOS) microchip technology to integrate an array of 78x56 potentiometric sensors, and a label-free reverse-transcriptase loop mediated isothermal amplification (RT-LAMP) assay. The platform communicates to a smartphone app which synchronises results in real time with a secure cloud server hosted by Amazon Web Services (AWS) for epidemiological surveillance. The assay on our LoC platform (RT-eLAMP) was shown to match performance on a gold-standard fluorescence-based real-time instrument (RT-qLAMP) with synthetic DENV-1 and DENV-2 RNA and extracted RNA from 9 DENV-2 clinical isolates, achieving quantitative detection in under 15 minutes. To validate the portability of the platform and the geo-tagging capabilities, we led our study in the laboratories at Imperial College London, UK, and Kaohsiung Medical Hospital, Taiwan. This approach carries high potential for application in low resource settings at the point-of-care (PoC).
Beykou M, Arias-Garcia M, Roumeliotis TI, et al., 2022, Proteomic characterisation of triple negative breast cancer cells following CDK4/6 inhibition, SCIENTIFIC DATA, Vol: 9
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- Citations: 2
Georgiou P, Moniri A, Moser N, et al., 2019, Devices and method for detecting an amplification event, WO2019234451A1
A method is disclosed herein for detecting an amplification reaction in a solution containing a biological sample using an array of ion sensors. The amplification reaction is indicative of the presence of a nucleic acid. The method comprises monitoring a signal from each respective sensor of the array of ion sensors, detecting a change in the signal from a first sensor of the array of ion sensors, and comparing the signal from the first sensor with the signal of at least one neighbouring sensor, the at least one neighbouring sensor being proximate to the first sensor in the array. The method further comprises determining, based on the comparing, that an amplification event has occurred in the solution in the vicinity of the first sensor.
Georgiou P, Yu L-S, Malpartida-Cardenas K, et al., 2019, Method for detecting a tandem repeat, WO2019234252A1
The present application relates to methods for detecting a tandem repeat in a nucleic acid sequence under isothermal conditions using primers.
Malpartida-Cardenas K, Miscourides N, Rodriguez-Manzano J, et al., 2019, Quantitative and rapid Plasmodium falciparum malaria diagnosis and artemisinin-resistance detection using a CMOS Lab-on-Chip platform, Biosensors and Bioelectronics, Vol: 145, ISSN: 0956-5663
Early and accurate diagnosis of malaria and drug-resistance is essential to effective disease management. Available rapid malaria diagnostic tests present limitations in analytical sensitivity, drug-resistance testing and/or quantification. Conversely, diagnostic methods based on nucleic acid amplification stepped forwards owing to their high sensitivity, specificity and robustness. Nevertheless, these methods commonly rely on optical measurements and complex instrumentation which limit their applicability in resource-poor, point-of-care settings. This paper reports the specific, quantitative and fully-electronic detection of Plasmodium falciparum, the predominant malaria-causing parasite worldwide, using a Lab-on-Chip platform developed in-house. Furthermore, we demonstrate on-chip detection of C580Y, the most prevalent single-nucleotide polymorphism associated to artemisinin-resistant malaria. Real-time non-optical DNA sensing is facilitated using Ion-Sensitive Field-Effect Transistors, fabricated in unmodified complementary metal-oxide-semiconductor (CMOS) technology, coupled with loop-mediated isothermal amplification. This work holds significant potential for the development of a fully portable and quantitative malaria diagnostic that can be used as a rapid point-of-care test.
Cacho-Soblechero M, Malpartida-Cardenas K, Moser N, et al., 2019, Programmable Ion-Sensing Using Oscillator-Based ISFET Architectures, IEEE SENSORS JOURNAL, Vol: 19, Pages: 8563-8575, ISSN: 1530-437X
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- Citations: 5
Moser N, Panteli C, Fobelets K, et al., 2019, Mechanisms for enhancement of sensing performance in CMOS ISFET arrays using reactive ion etching, Sensors and Actuators B: Chemical, Vol: 292, Pages: 297-307, ISSN: 0925-4005
In this work, we investigate the impact of successively removing the passivation layers of ISFET sensors implemented in a standard CMOS process to improve sensing performance. Reactive ion etching is used as a post-processing technique of the CMOS chips for uniform and accurate etching. The removal of the passivation layers addresses common issues with commercial implementation of ISFET sensors, including pH sensitivity, capacitive attenuation, trapped charge, drift and noise. The process for removing the three standard layers (polyimide, Si3N4 and SiO2) is tailored to minimise the surface roughness of the sensing layer throughout an array of more than 4000 ISFET sensors. By careful calibration of the plasma recipe we perform material-wise etch steps at the top and middle of the nitride layer and top of the oxide layer. The characterisation of the ISFET array proves that the location of the trapped charge in the passivation layers is mainly at the interface of the layers. Etching to the top of the oxide layer is shown to induce an improvement of 80% in the offset range throughout the array and an increase in SNR of almost 40 dB compared to the non-processed configuration. The performance enhancement demonstrates the benefit of a controlled industry-standard etch process on CMOS ISFET array system-on-chips.
Tripathi P, Moser N, Georgiou P, 2019, A Neuron-Based ISFET Array Architecture with Spatial Sensor Compensation, IEEE International Symposium on Circuits and Systems (IEEE ISCAS), Publisher: IEEE, ISSN: 0271-4302
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- Citations: 5
Rodriguez-Manzano J, Miscourides N, Malpartida-Cardenas K, et al., 2019, Rapid detection of <i>Klebsiella pneumoniae</i> using an auto-calibrated ISFET-array Lab-on-Chip platform, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, ISSN: 2163-4025
Moser N, Keeble L, Rodriguez-Manzano J, et al., 2019, ISFET Arrays for Lab-on-Chip Technology : A Review, 26th IEEE International Conference on Electronics, Circuits and Systems (ICECS), Publisher: IEEE, Pages: 57-60
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- Citations: 14
Cicatiello C, Moser N, Boutelle M, et al., 2019, Live Demonstration : A Portable Multi-Ion Platform with Integrated Microfluidics, IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, ISSN: 2163-4025
Au A, Moser N, Rodriguez Manzano J, et al., 2018, Live demonstration: a mobile diagnostic system for rapid detection and tracking of infectious diseases, 2018 IEEE International Symposium on Circuits and Systems (ISCAS), ISSN: 2379-447X
Moser N, Petrou L, Hu Y, et al., 2018, An ISFET Pixel with Integrated Trapped Charge Compensation using Temperature Feedback, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, ISSN: 0271-4302
Abdulwahab M, Moser N, Rodriguez Manzano J, et al., 2018, A CMOS Bio-Chip combining pH Sensing, Temperature Regulation and Electric Field Generation for DNA Detection and Manipulation, 2018 IEEE International Symposium on Circuits and Systems (ISCAS), ISSN: 2379-447X
Moser N, Rodriguez-Manzano J, Lande TS, et al., 2018, A scalable ISFET sensing and memory array with sensor auto-calibration for on-chip real-time DNA detection, IEEE Transactions on Biomedical Circuits and Systems, Vol: 12, Pages: 390-401, ISSN: 1932-4545
This paper presents a novel CMOS-based system-onchip with a 78 × 56 ion-sensitive field-effect transistor array using in-pixel quantization and compensation of sensor nonidealities. The pixel integrates sensing circuitry and memory cells to encode the ion concentration in time and store a calibration value per pixel. Temperature sensing pixels spread throughout the array allow temperature monitoring during the reaction. We describe the integration of the array as part of a lab-on-chip cartridge that plugs into a motherboard for power management, biasing, data acquisition, and temperature regulation. This forms a robust ion detection platform, which is demonstrated as a pH sensing system. We show that our calibration is able to perform readout with a linear spread of 0.3% and that the system exhibits a high pH sensitivity of 3.2 μs/pH. The complete system is shown to perform on-chip realtime DNA amplification and detection of lambda phage DNA by loop-mediated isothermal amplification.
Moser N, Rodriguez-Manzano J, Yu L-S, et al., 2017, Live Demonstration: A CMOS-Based ISFET Array for Rapid Diagnosis of the Zika Virus, IEEE International Symposium on Circuits and Systems (ISCAS) 2017, ISSN: 2379-447X
We demonstrate a diagnostics platform which integrates an ISFET array and a temperature control loop for isothermal DNA detection. The controller maintains a temperature of 63◦C to perform nucleic acid amplification which is detected by the on-chip sensors. The 32x32 ISFET array is first calibrated to cancel trapped charge and then measures the change in the pH of the reaction. The sensor data is sent to a microcontroller and the reaction is monitored in real-time using a MATLAB interface. Experiments confirm a change of 0.9 pH when tested for the presence of RNA associated with the Zika virus.
Moser N, Panteli C, Ma D, et al., 2017, Improving the pH Sensitivity of ISFET Arrays withReactive Ion Etching, BioCAS 2017, Publisher: IEEE
In this paper, we report a method to improvesensitivity for CMOS ISFET arrays using Reactive Ion Etching(RIE) as a post-processing technique. The process etches awaythe passivation layers of the commercial CMOS process, using anoxygen (O2) and sulfur hexafluoride (SF6) plasma. The resultingattenuation and pH sensitivity are characterised for five diesetched for 0 to 15 minutes, and we demonstrate that capacitiveattenuation is reduced by 196% and pH sensitivity increasedby 260% compared to the non-etched equivalent. The spread oftrapped charge is also reduced which relaxes requirements on theanalogue front-end. The technique significantly improves the performanceof the fully-integrated sensing system for applicationssuch as DNA detection.
Hu Y, Moser N, Georgiou P, 2017, A 32 x 32 ISFET Chemical Sensing Array With Integrated Trapped Charge and Gain Compensation, IEEE SENSORS JOURNAL, Vol: 17, Pages: 5276-5284, ISSN: 1530-437X
This paper presents a CMOS-based 32 × 32 ion-sensitive field-effect transistor (ISFET) system-on-chip for real-time ion imaging. Fabricated in an unmodified 0.35-μm CMOS technology, the ISFET sensor array is based on a pixel topology, which uses capacitive feedback to improve signal attenuation due to passivation capacitance and a low-leakage floatinggate reset followed by a digital correlated double sampling to robustly remove unwanted trapped charge-induced dc offset. An automatic gain calibration (AGC) is used to perform realtime calibration and guarantee all sensors that have the same gain with a 99% accuracy, and combining all these mechanisms guarantees an average pixel voltage variation of 14.3 mV after gain is applied when measured over multiple dies. The full array is experimentally shown to be capable of real-time ion imaging of pH, with an intrinsic sensitivity of 39.6mV/pH and a scan rate of 9.3 frames/s when running the AGC, with a total power consumption of 10.2 mW.
Moser N, Leong CL, Hu Y, et al., 2017, Live Demonstration: Real-Time Chemical Imaging of Ionic Solutions Using an ISFET Array, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, ISSN: 0271-4302
Moser N, Lande TS, Toumazou C, et al., 2016, ISFETs in CMOS and Emergent Trends in Instrumentation: A Review, IEEE Sensors Journal, Vol: 16, Pages: 6496-6514, ISSN: 1530-437X
Over the past decade, ion-sensitive field-effect transistors (ISFETs) have played a major role in enabling the fabrication of fully integrated CMOS-based chemical sensing systems. This has allowed several new application areas, with the most promising being the fields of ion imaging and full genome sequencing. This paper reviews the new trends in front-end topologies toward the design of ISFET sensing arrays in CMOS for these new applications. More than a decade after the review of the ISFET by Bergveld which summarized the state of the art in terms of device and early readout circuity, we describe the evolution in terms of device macromodel and identify the main sensor challenges for current designers. We analyze the techniques that have been reported for both ISFET instrumentation and compensation, and conclude that topologies are focusing on device adaptation for offset and drift cancellation, as opposed to system compensation which are often not as robust. Guidelines are provided to build a tailored CMOS ISFET array, emphasizing that the needs in terms of applications are the keys to selecting the right pixel architecture. Over the next few years, the race for the largest and densest array is likely to be put on hold to allow the research to focus on new pixel topologies, ultimately leading to the development of reliable and scalable arrays. A wide range of new applications are expected to motivate this paper for at least another decade.
Moser N, Leong CL, Hu Y, et al., 2016, An Ion Imaging ISFET Array for Potassium and Sodium Detection, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 2847-2850, ISSN: 0271-4302
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- Citations: 17
Lallement G, Moser N, Geondou P, 2016, Bio-inspired pH sensing using Ion Sensitive Field Effect Transistors, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 2835-2838, ISSN: 0271-4302
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- Citations: 2
Moser N, Lande TS, Georgiou P, 2016, A Robust ISFET Array with In-Pixel Quantisation and Automatic Offset Calibration, 12th IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, Pages: 50-53, ISSN: 2163-4025
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- Citations: 8
Moser N, Lande TS, Georgiou P, 2016, Scaling ISFET Instrumentation with In-Pixel Quantisation to Deep Submicron Technologies, 12th IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, Pages: 436-439, ISSN: 2163-4025
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- Citations: 7
Douthwaite M, Moser N, Koutsos E, et al., 2016, A CMOS ISFET Array for Wearable Thermoelectrically Powered Perspiration Analysis, 12th IEEE Biomedical Circuits and Systems Conference (BioCAS), Publisher: IEEE, Pages: 54-57, ISSN: 2163-4025
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- Citations: 3
Moser N, Lande TS, Georgiou P, 2015, A Novel pH-to-Time ISFET Pixel Architecture with Offset Compensation, IEEE International Symposium on Circuits and Systems (ISCAS), Publisher: IEEE, Pages: 481-484, ISSN: 0271-4302
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- Citations: 15
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